This is a revised research grant application. The long range objective of this research effort is to establish the incidence of stroke related to use/abuse of illicit and over-the-counter, (OTC), sympathomimetic drugs. The specific aims are: 1) establish comparative proportions of drug use/abuse in patients presenting with acute stroke and other illnesses in the population served by the University of Maryland and Veterans Administration Hospitals; 2) determine the relative risk of stroke attributable to use/abuse of illicit and OTC sympathomimetic drugs; 3) develop a questionnaire to ascertain patterns of drug use in acute stroke patients and correlate with pharmacokinetic data and type of stroke; 4) compare drug use patterns assessed by the questionnaire with the results of toxicologic screens; 5) define the temporal relationship between drug use and stroke onset; and 6) define potential interactions between exposure to individual drugs and other drugs (even "innocent" drugs) as well as pre-existing stroke risk factors. Experimental design consists of a 1:2 case:control study methodology and will compare stroke patients with patients presenting with emergent medical/surgical conditions. Exclusion criteria include conditions known to be associated with illicit drug use. A Confidentiality Certificate will protect all research subjects from civil, criminal, administrative and legal scrutiny. Statistical analysis will provide the relative odds for drug exposure and stroke and (possibly) for each specific stroke subtype. Interactions between use of drug(s) and presence of other drugs and/or stroke risk factors will be sought by a variety of techniques. Preliminary observations will be made to assess the effect of the latency between and chronicity of exposure. The project has clear public health implications in terms of improved understanding of stroke mechanisms, impact on use of promising therapies for acute stroke, and public education and preventative programs.